DOI: 10.

1177/0004563219867989

The Preanalytical Phase – Past Present and Future.

Journal: Annals of Clinical Biochemistry

Manuscript ID ACB-19-187

Manuscript Type: Editorial

Date Submitted by the

11-Jul-2019
Author:

Complete List of Authors: Cornes, Michael; Worcestershire Acute Hospitals NHS Trust, Biochemistry

Keywords: Laboratory management < Laboratory methods

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3 The Preanalytical Phase – Past Present and Future
4
5
6
7 Dr Michael Cornes
8 Consultant Clinical Scientist & Pathology Clinical Director, Biochemistry Department,
9 Worcestershire Acute Hospitals NHS Trust, Worcester, WR5 1DD
10 Email: michael.cornes@nhs.net
11
12
13 DECLARATIONS
14
15 Conflicts of interest: a full member of the EFLM working group for the pre-analytical phase
16 (EFLM-WG-PRE) and the ACB working group for the pre-analytical phase (ACB-WG-PRE)
17 Funding: This research received no specific grant from any funding agency in the public,
18 commercial, or not-for-profit sectors.
19
Ethical approval: Not applicable
20
21 Guarantor: MC
22 Contributorship: MC sole author
23 Acknowledgements: None
24
25
26 In the brain to brain loop described by George Lundberg1 the preanalytical phase is
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defined as all parts of the total testing process (TTP) that occur from the conception of the
29 requirement for the test through obtaining of the sample, transport to the laboratory, and
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31 sample preparation, to the point where the sample is ready for analysis. It is widely agreed
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33 that 60-70% of the errors that occur in laboratory medicine are attributable to the
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preanalytical phase. The term preanalytical phase first appeared in the literature in a paper by
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36 Statland and Winkel in 1977.2 Since then interest in the preanalytical phase has grown: the
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38 frequency of the keyword ‘preanalytical’ in PubMed has increased to ~ 160 occurrences in
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40 2018. In fact, the term ‘laboratory error’ first occurred even earlier than this in 19543 and
41 since then it has been apparent that the majority of laboratory errors occur in the preanalytical
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43 phase, presumably because these steps involve more human tasks and are therefore more
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45 prone to errors.4 As a profession we have achieved exceptionally high standards in the
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analytical phase and are now striving to ensure that the quality outside of the laboratory is at
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48 the same level.
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50 In his paper on the history of the preanalytical phase5 Walter Guder describes the first
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52 preanalytical issue that he had to address, the earliest described pre-analytical ‘case’: samples
53 from a certain location had higher rates of haemolysis than other locations. It transpired that
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55 the problem was due to contamination of samples with rain water as they were carried across
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57 a yard to the laboratory. This is not a problem that would be encountered in the modern
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laboratory since the widespread adoption of closed blood collection in the early 1970s.6
60 Numerous advances in equipment have helped improve the quality and stability of samples,

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3 These include urine collection devices in the middle ages, the introduction of basic blood
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5 tubes in the 1800s, centrifugation in the 1850s, anticoagulants in the 1930s, serum separators
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7 in the 1990s and finally, phlebotomy safety devices to avoid needlestick injuries in the
8
9
2000s.6 However, the impacts of these earlier technological advances are unclear as error
10 rates have only been documented more recently. One innovation with proof of improvement
11
12 is the implementation of electronic patient identification which has been shown to reduce
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14 wrong blood in tube errors up to five fold.7
15
In the 1990s Mario Plebani and the IFCC WG LEPS (International Federation for
16
17 Clinical Chemistry Working Group for Laboratory Error and Patient Safety) began a project
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19 to document the types and frequencies of errors seen in a laboratory.8 Once documented they
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21 put in place processes to improve the error rates and reperformed the study 10 years later.9
22 They demonstrated that by monitoring key performance indicators (KPIs) in the preanalytical
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24 phase they significantly reduced error frequency from 0.47% to 0.309%. They further
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26 progressed this work and have been developing and evolving KPIs in the preanalytical phase,
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producing guidelines on what laboratories should be monitoring and providing tools that can
29 be used to do so.10
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31 This idea of monitoring the preanalytical phase brings us to where we are now. As a
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33 profession, awareness and interest in the preanalytical phase is at its highest level ever.
34
Through the requirement in ISO15189, the work of the IFCC WG LEPS and the EFLM WG-
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36 PRE (European Federation for Laboratory Medicine working group for the Preanalytical
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38 Phase) 94% of laboratories now collect data relating to quality in the preanalytical phase and
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40 are aware that the majority of laboratory errors occur in this phase.11 There have been a series
41 of European biannual conferences organised by the EFLM WG PRE discussing the
42
43 preanalytical phase and from these, eight preanalytical aspects were identified, prioritised for
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45 standardisation and the progress made was summarised in 2016.12 The successfully addressed
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issues covering some of these areas include:
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48  Venous blood sampling for which a recent EFLM guideline on venous phlebotomy
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50 has been produced13
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52  Quality indicators for the pre-analytical phase10
53
54  Recommendations on standardised fasting requirements14
55  Recommendations on patient identification15
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57  Recommendations on Order of Draw16
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59 The areas where work is on-going include:
60

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 test ordering appropriateness
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5  managing unsuitable specimens
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7  sample stability
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9  Paediatric/neonatal blood sampling guidance
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12 However, the production of guidelines and recommendations is not sufficient. The CLSI
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14 Guideline GP41 has clear guidance around patient identification, yet there is still a failure to
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16 do this correctly in 16.1% of cases.17 Laboratorians now need to work together to promote the
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implementation of these guidelines and technologies to achieve the required level of
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19 performance.
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21 There are a number of on-going projects which address how we process and act upon the
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23 information we are collecting. If we are not going to act on the information we have, there is
24 little point in collecting it. In order to address this there have been separate surveys issued by
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26 the EFLM WG PRE and the ACB WG PRE to collect information on the current situation
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28 across the UK and Europe.11,18,19 These showed that 94% of 1347 participants collected data
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on preanalytical errors. However, 31% of those collecting data did no further analysis, and of
31 those that did 33% took no further action regardless of the findings. Additionally, how and
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33 what data are collected and counted can vary.18 The ACB WG PRE reviewed the various
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35 options for collecting data, recommending that when possible the laboratory information
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management system should be used as the recording tool.20 Even for the most commonly
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38 assessed preanalytical indicator, the Haemolysis, Icteric, Lipaemic (HIL) indices, there is
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40 significant variation in how the results of these indices are handled, ranging from simply
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42 documenting the findings through to rejecting the whole sample. From these studies it is
43 hoped that best practice guidelines will emerge so that the process can either be harmonised,
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45 or at the very least ensure the there is a robust evidence base to support the approach of an
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47 individual laboratory.11
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The major challenge the laboratory has in addressing the issues in the preanalytical phase
50 is to successfully target the staff involved in pre-analytical sample handling. These staff
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52 generally work outside the laboratory environment and often are not managed by the
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54 laboratory. It is essential that for these staff groups there is appropriate and on-going
55 education on correct sample collection and handling procedures and on the implications of
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57 errors in the preanalytical phase. This may be via direct education sessions, eLearning or via
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59 direct feedback through sample reports or verbally.12,21
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3 Some tests require specific patient preparation e.g. fasting or other lifestyle or medication
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5 adjustment for a period prior to testing. The execution and documentation of this is often
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7 poorly executed. The EFLM WG PRE has published guidance to standardise fasting time but
8
9
currently there are few guidelines or manuscripts summarising how other factors can
10 influence results and how they can be standardised to minimise their influence.14 Such factors
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12 include medications, over the counter drugs, herbal remedies, physical activity levels etc.
13
14 One of the biggest factors that might influence the quality of a sample is the journey
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of the sample to the laboratory. Currently there is a raft of evidence on sample stability which
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17 is frequently conflicting or non-standardised. The conditions in which a sample is
18
19 transported are often very variable, particularly with respect to time, temperature and light
20
21 exposure. One of the key areas of focus over the immediate future will be to improve the
22 quality of reporting of sample stability studies. This should mean that future studies will
23
24 provide sufficient information to allow transfer of the findings to other appropriate healthcare
25
26 settings. Standardisation of reporting has the potential to allow collation of data into one large
27
28
database. The technology to standardise, monitor and control the variables involved in
29 transport procedures already exists but is not used routinely due to the costs involved.
30
31 Moving forward from the KPI work discussed above, if laboratory medicine is to
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33 truly move to a point where quality in the preanalytical phase is as well controlled as in the
34
analytical phase, then participation in peer comparison schemes via EQA providers will be an
35
36 important driver. This will enable laboratories that are outliers in terms of preanalytical EQA
37
38 performance to critically assess the quality of their preanalytical phase or their monitoring of
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40 it. The interpretation of performance compared to peers is perhaps more complex than for
41 other EQA schemes: laboratories flagged as having fewer pre-analytical errors than its peers
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43 may indicate either excellent performance or alternatively incomplete detection and capture
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45 of preanalytical errors. The converse may be true for laboratories having higher pre-analytical
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rates than peers. It is hoped that careful and considered use of pre-analytical EQA
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48 performance data may drive up standards and help embed pre-analytical quality in the culture
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50 of the laboratory. While it is evident that we are taking steps in the right direction, recent
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52 surveys illustrate that we are not yet where we need to be.11,19
53 One final and important factor is the improvement of the appropriateness of test
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55 ordering. There are many on-going projects in this field with the most promising ideas being
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57 around condition specific requesting or via reflex driven algorithms. This also covers
58
59
reducing the use of repeated testing within inappropriate timeframes.
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3 The future requires us to embed existing guidelines into routine practice and to audit
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5 their impact. This will produce the evidence base to support the development of further
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7 guidelines in areas where there is gap in our knowledge. To improve the service we provide
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to our patients, laboratories must not only monitor performance in the pre-analytical phase
10 but take corrective action where necessary to improve performance. This will require a
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12 collaborative approach with users of laboratory medicine to improve the quality of the patient
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14 experience.
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3 The Preanalytical Phase – Past Present and Future
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5
6 References
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57 Kjell Grankvist9, Joao Tiago Guimaraes10, Gunn B.B. Kristensen11, Barbara de la
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Part 1: How do European laboratories monitor the preanalytical phase? On behalf of

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3 the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)
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5 Working Group for the Preanalytical Phase (WG-PRE) Biochemia Medica 2019 AOP
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